African Trypanosomes cause fatal disease in man (sleeping sickness) and cattle (wasting disease). Human serum lyses the animal infective form, Trypanosoma brucei brucei (T.b.brucei), but not the human infective forms. There are two distinct trypanolyticfactors (TLFs) called TLF1 and TLF2 in human serum that are responsible for this killing. Both TLFs contain haptoglobin related protein (hpr). Hpr is considered the toxin in the TLFs and may also be the ligand for a parasite receptor for TLF1. Understanding the mechanisms of lysis of T.b.brucei may lead to the development of therapeutic control methods against trypanosomiasis. Hpr will be expressed recombinantly in different forms: the TLF form, a distinct form present in cancer sera, as separate hpr subunits, and as a secreted hpr form. The recombinant proteins will be analyzed for fulfilling the following specific aims: (1) to address the role of hpr in trypanolysis (Is it the toxin?) (2) to use the recombinant protein for its role as a ligand, and for isolation of the parasite receptor for TLF1. Knowledge of the role hpr plays in trypanolysis may enable us to develop hpr-based fusion toxin, or vaccine against the receptor. Isolation of native hpr from TLF would be ideal for these studies, but the labile and multicomponent nature of TLFs makes it extremely difficult to isolate an active, native hpr, hence the recombinant approach.